Mercado-Perez, Arnaldo

The intestinal epithelium is exposed to diverse combinations of microbiota-derived compounds; however, the mechanisms by which the host integrates these signals remain poorly defined. Studying two highly abundant microbial metabolites, we identified the purine metabolite hypoxanthine as an effector metabolite that directly drives signaling and the short-chain fatty acid butyrate as a regulatory metabolite that conditions host responsiveness. Specifically, hypoxanthine activates the adenosine A1 receptor–TRPC4 axis in enterochromaffin (EC) cells, triggering calcium influx and serotonin release resulting in accelerated gastrointestinal transit locally and increased platelet activation systemically. In contrast, butyrate epigenetically upregulates specific G protein–coupled receptors and ion channels to enhance response to hypoxanthine and the neurotransmitters norepinephrine and dopamine. These findings define a cooperative signaling framework and highlight the role of EC cells as a distinct epithelial signaling hub that senses and integrates microbial metabolite signals to drive physiological responses. Our findings provide a mechanistic foundation for therapeutic strategies that leverage combinatorial microbial signaling.

Background: Mechanically gated PIEZO channels lead to an influx of cations, activation of additional Ca2+ channels, and cell depolarization. This study aimed to investigate PIEZO2’s role in breast cancer. Methods: The clinical relevance of PIEZO2 expression in breast cancer patient was analyzed in a publicly available dataset. Utilizing PIEZO2 overexpressed breast cancer cells, and in vitro and in vivo experiments were conducted. Results: High expression of PIEZO2 was correlated with a worse survival in triple-negative breast cancer (TNBC) but not in other subtypes. Increased PEIZO2 channel function was confirmed in PIEZO2 overexpressed cells after mechanical stimulation. PIEZO2 overexpressed cells showed increased motility and invasive phenotypes as well as higher expression of SNAIL and Vimentin and lower expression of E-cadherin in TNBC cells. Correspondingly, high expression of PIEZO2 was correlated with the increased expression of epithelial–mesenchymal transition (EMT)-related genes in a TNBC patient. Activated Akt signaling was observed in PIEZO2 overexpressed TNBC cells. PIEZO2 overexpressed MDA-MB-231 cells formed a significantly higher number of lung metastases after orthotopic implantation. Conclusion: PIEZO2 activation led to enhanced SNAIL stabilization through Akt activation. It enhanced Vimentin and repressed E-cadherin transcription, resulting in increased metastatic potential and poor clinical outcomes in TNBC patients.

AbstractBackgroundCurrent options for the reduction of acne scarring (eg, ablative laser resurfacing) are associated with considerable side effects and limitations in terms of patient population. Percutaneous collagen induction via microneedling poses an alternative treatment method due to its low rates of reported adverse events and side effects.ObjectiveTo assess the safety and effectiveness of microneedling treatments in reducing acne scars.MethodsA total of 22 patients (18 females and 4 males) with a mean age of 38 ± 7.6 years were assessed regarding the appearance of facial acne scarring. Acne scars were assessed via the Acne Scar Assessment Scale (ASAS) and the Goodman and Baron acne scar grading scale before and after two/three treatments. Additionally, the post‐interventional development of side reactions, adverse events, and patient‐reported outcomes (eg, pain/discomfort, skin redness) was reported.ResultsCompared to baseline, the mean ASAS value was improved statistically significantly on average by 1.41 and 1.46 after the second treatment as assessed by the independent raters and the patients, respectively. In patients who received a total of three treatments, a statistically significant mean improvement in ASAS value of 1.35 and 1.66 compared to baseline was assessed by the independent raters and patients, respectively. No unexpected adverse events were reported. The severity and rate of side reactions decreased over the course of this study.ConclusionMicroneedling treatments can pose a safe and effective option in the reduction of acne scarring. In this study, microneedling helped achieving a significant reduction of acne scars while showing high patient safety.

Abstract Background Facial aging is a multifactorial process that involves all tissues of the face, including skin, muscles, fat, ligaments, and bone. Whereas robust evidence is available for age-related changes of bone and facial fat, the influence of age on facial muscle activity is poorly understood. Objectives The objective of this study was to investigate the motor unit action potential of facial muscles by utilizing surface-derived, noninvasive electromyography in young and old healthy volunteers. Methods The study investigated a total of 32 healthy volunteers with a mean [standard deviation] age of 42.6 [19.6] years (range, 21-82 years) and a mean BMI of 23.9 [2.7] kg/m2 (range, 18.5-29.7 kg/m2) by performing surface-derived, noninvasive facial electromyography. Nine facial muscles were investigated bilaterally, resulting in a total of 1632 measurements of the signal, baseline noise, and signal-to-noise ratio of these muscles. Results The results of the study revealed that age does not significantly influence the signal (P = 0.234), the baseline noise (P = 0.225), or the signal-to-noise ratio (P = 0.432) of younger individuals (<30 years) vs older individuals (>50 years) in a gender- and BMI-matched statistical model. Exceptions were the zygomaticus major muscle (reduced activity), procerus muscle (increased activity), and corrugator supercilii muscle (increased activity). Conclusions The results of this facial electromyography study may help to increase the understanding of facial aging. Future studies need to reproduce the results presented herein to further increase our understanding of facial aging.